Medical research is entering an era in which the key advancements in our understanding of the origin and nature of disease will occur primarily at the molecular and genetic level. Medical imaging technologies will play an important role by enabling us to follow these processes in the context of the live organism. Because its genetic profile is now well understood and can be manipulated, the mouse provides a powerful tool for modeling a variety of human diseases. Important areas of investigation include localization and quantification of gene expression, identification of cancer metastasis, longitudinal evaluation of therapeutic protocols, characterization of phenotype in transgenic mice, and understanding of the biodistribution and efficacy of new pharmaceuticals. However, new imaging devices with very high spatial resolution will be required for these tasks. In this proposed project, technologies developed during the previous funding period for breast imaging will be applied to the development of a dual modality tomograph for small animal research. The tomograph is designed to simultaneously acquire 3D x-ray transmission (CT) and 3D gamma emission (SPECT) data at high spatial resolution, thereby providing spatially and temporally coregistered structural and functional volumetric data. Our goal is to develop a unique tool for repeated, non-invasive measurement of cellular and molecular processes in small animals. The specific aims of the project are to: 1. Build an x-ray CT scanner using CCD-based x-ray detector modules optimized for fast readout and high spatial resolution 2. Build a pinhole SPECT system designed to minimize spatial resolution loss from pinhole penetration and from depth-of-interaction blurring effects 3. Develop software and design phantoms for calculation and empirical verification of multimodality spatial resolution, sensitivity, and acquisition time for various tomograph parameter values 4. Use mathematical and physical phantoms to evaluate 3D cone beam reconstruction techniques 5. Construct and characterize an integrated system, combining the CT and SPECT systems on a single gantry.